Drug-Drug Interaction Study of MDR-001 With Rifampin and Itraconazole in Healthy Adult Participants

Официальное название

A Phase 1 Study to Evaluate the Effect of Rifampin on the Pharmacokinetics of MDR-001 and the Effect of Itraconazole on the Pharmacokinetics of MDR-001 in Healthy Adult Study Participants

Обзор

A Phase I, open-label, fixed-sequence, two-part drug-drug interaction study in healthy Chinese adults to evaluate the effect of multiple-dose rifampin (Part A) or itraconazole (Part B) on the single-dose pharmacokinetics of MDR-001, an oral GLP-1 receptor agonist.

Подробное описание

This phase 1, single-center, open-label, fixed-sequence drug-drug interaction study will evaluate the effect of multiple-dose rifampicin (a strong CYP3A4 inducer) and multiple-dose itraconazole (a strong CYP3A4 inhibitor) on the single-dose pharmacokinetics of MDR-001, an oral small-molecule GLP-1 receptor agonist being developed for weight management. The study plans to enroll 28 healthy Chinese adults (18-55 years, BMI 18-28 kg/m²), with 12 participants in Part A (rifampicin) and 16 in Part B (itraconazole). The primary outcomes are the effects of rifampicin and itraconazole on Cmax, AUC0-t, and AUC0-∞ of MDR-001. Secondary outcomes include safety and tolerability (adverse events, vital signs, ECG, laboratory tests) and comparison of other pharmacokinetic parameters (Tmax, t1/2, MRT, CL/F, Vd/F, λz) between MDR-001 alone and combined with the interacting drugs.

Вмешательства

• Препарат MDR-001
  Oral small-molecule GLP-1 receptor agonist ;Investigational drug (not yet approved)
• Препарат Rifampin
  Strong CYP3A4 inducer; Marketed anti-tuberculosis drug
• Препарат Itraconazole
  Strong CYP3A4 inhibitor; Marketed antifungal drug

Первичные конечные точки

• Cmax of MDR-001 [Срок оценки: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).]
• AUC0-t of MDR-001 [Срок оценки: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).]
• AUC0-∞ of MDR-001 [Срок оценки: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).]

Вторичные конечные точки (12)

• Other Pharmacokinetic Parameters of MDR-001 [Срок оценки: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).]
• Other Pharmacokinetic Parameters of MDR-001 [Срок оценки: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).]
• Other Pharmacokinetic Parameters of MDR-001 [Срок оценки: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).]
• Other Pharmacokinetic Parameters of MDR-001 [Срок оценки: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).]
• Other Pharmacokinetic Parameters of MDR-001 [Срок оценки: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).]
• Other Pharmacokinetic Parameters of MDR-001 [Срок оценки: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).]
• Safety and Tolerability - Adverse Events [Срок оценки: From first dose of study drug (Day 1) through follow-up phone call (Day 19 ±2 for Part A, Day 16 ±2 for Part B).]
• Safety and Tolerability - Clinical Laboratory Tests [Срок оценки: Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.]
• Safety and Tolerability - Clinical Laboratory Tests [Срок оценки: Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.]
• Safety and Tolerability - Clinical Laboratory Tests [Срок оценки: Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.]
• Safety and Tolerability - Clinical Laboratory Tests [Срок оценки: Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.]
• Safety and Tolerability - Clinical Laboratory Tests [Срок оценки: Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.]

Критерии участия

Критерии включения

• Voluntary participation and signed informed consent before any study procedures, with full understanding of the study content, procedures, and potential adverse reactions.
• Healthy Chinese adult males or females aged 18 to 55 years (inclusive).
• Body weight ≥50 kg for males and ≥45 kg for females, and body mass index (BMI) between 18 and 28 kg/m² (inclusive).
• Judged by the investigator to be in good health, with medical history, laboratory tests, physical examination, vital signs, and ECG results being normal or abnormal without clinical significance.
• Participants and their partners must have no pregnancy plan and agree to use effective non-drug contraceptive measures (e.g., condoms, non-medicated intrauterine devices) from 2 weeks before screening until 6 months after the end of the study, unless permanent sterilization has been performed (e.g., bilateral tubal ligation, vasectomy).
• Willing to comply with the visit schedule, study treatment, laboratory tests, and other study-related procedures and requirements as specified in the protocol.

Критерии исключения

• Average daily smoking >5 cigarettes within 3 months before dosing.
• History of headaches (e.g., migraine, tension-type headache).
• Allergic constitution (multiple drug or food allergies) or intolerance/allergy to the active ingredient or excipients of the study drugs.
• History of alcohol abuse (≥14 units of alcohol per week; 1 unit = 285 mL beer, 25 mL spirits, or 100 mL wine).
• History of drug abuse or use of illicit drugs within 5 years before dosing.
• Blood donation or significant blood loss (≥400 mL) within 3 months before dosing, or planned blood donation during the study.
• Any disease that increases bleeding risk, such as acute gastritis or gastric/duodenal ulcer.
• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2), or genetic conditions predisposing to MTC.
• History of pancreatitis or symptomatic gallbladder disease.
• Serum calcitonin > upper limit of normal (ULN) at screening.
• Dysphagia, or gastrointestinal disorders affecting absorption (e.g., diarrhea, vomiting, inflammatory bowel disease, active ulcer), or history of gastrointestinal surgery leading to malabsorption, or long-term use of drugs affecting gastrointestinal motility (e.g., bariatric surgery such as gastric banding).
• Special dietary requirements and unable to accept standardized meals.
• Surgery within 3 months before dosing, or planned surgery during the study, or surgery that affects drug absorption, distribution, metabolism, or excretion.
• Received live attenuated vaccine within 1 month before dosing, or planned vaccination during the study.
• Use of any prescription drug, over-the-counter drug, vitamin product, or herbal medicine within 14 days before dosing.
• Significant changes in diet or exercise habits within 3 months before dosing.
• Use of CYP3A4 inhibitors, CYP3A4 inducers, or P-gp inhibitors within 14 days before the first dose, or planned use during the study.
• Participation in another clinical trial or receipt of an investigational drug within 3 months before dosing (unless the participant withdrew before treatment/randomization).
• ECG abnormalities with clinical significance at screening; QTcF >450 msec (males) or >470 msec (females) by Fridericia's correction.
• Pregnant, lactating, or positive pregnancy test in females of childbearing potential.
• Clinically significant laboratory abnormalities, or clinically significant diseases within 12 months before dosing (respiratory, circulatory, digestive, endocrine, rheumatic/immune, nervous, hematologic, or psychiatric disorders) that make the participant unsuitable for the study.
• Positive screening for hepatitis B surface antigen, hepatitis C antibody/core antigen, HIV antibody, or syphilis antibody.
• Acute illness or concomitant medication between screening and first dose.
• Positive alcohol breath test or urine drug screen.
• Any other condition judged by the investigator as unsuitable for participation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Китай · 1 центр

• The First Hospital of Jilin University — Changchun

Идентификаторы

NCT: NCT07550621 · MDR-001-CN-06

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗